Recent reporting of the 9 year follow-up for the TAILORx trial suggests that there may be no benefit with adjuvant chemotherapy for ER +, HER2 -, N(0) breast cancer patients with a Oncotype DX® (ODX) recurrence score (RS) <26. Since endocrine therapy for this group of patients who comply with treatment still results in distant recurrence (rMBC) in 3% and 5% of the ODX low and ODX intermediate risk groups at 9 years, respectively, we are motivated to help find early treatments for these patients by identifying their recurrence risk at diagnosis with improved risk stratification.

Methods: Optical Prediction of Time Interval to Metastasis (OPTIM), a novel assay, prognostic for rMBC, is based on an intrinsic optical signature from collagen, derived from the average of point by point ratios of forward to backward (F/B) second harmonic generation (SHG) light scatter that is sensitive to form and structure of fibrillar collagen in the extracellular matrix of archival tissue microarray samples. (Burke et al. BMC Cancer 15 (2015): 929). The 125 patients in this cohort were part of a clinical trial, looking for genomic predictors of rMBC in untreated patients, so we were able to calculate a surrogate 21-gene RT-PCR assay (S-ODX) value based on gene expression data available through NCBI GEO database (Gyorffy et al. Breast Cancer Res Treat (2012) 132:1025). We analyzed these patient's rMBC outcomes using logistic regression and Kaplan-Meier (KM) analysis.

Results: OPTIM alone stratified at 2.5X relative risk (RR) between quartiles Q1 and Q4, similar to S-ODX low vs high recurrence score (RS) groups (from TAILORx Trial) with 2.8X RR. Using quartiles of OPTIM vs S-ODX together we stratify patients to recurrence risk (rMBC/at Risk), with an improved risk stratification of 5X RR in the RS<26 low risk groups.

OPTIM Quartiles vs RS Risk Groups in TAILORx Trial

S-ODX →High (RS>25) Intermediate (RS 11-25) Low (RS <11) All 
OPTIM↓ ↓ ↓ ↓ 
Q1 7/9 7/12* 5/10 19/31* 
Q2 5/9 5/14 2/8 12/31 
Q3 8/12*** 1/8 1/11*** 10/31 
Q4 6/10** 2/17* 0/5** 8/32* 
All 26/40*** 15/51 8/34*** 49/125 
S-ODX →High (RS>25) Intermediate (RS 11-25) Low (RS <11) All 
OPTIM↓ ↓ ↓ ↓ 
Q1 7/9 7/12* 5/10 19/31* 
Q2 5/9 5/14 2/8 12/31 
Q3 8/12*** 1/8 1/11*** 10/31 
Q4 6/10** 2/17* 0/5** 8/32* 
All 26/40*** 15/51 8/34*** 49/125 

Recurrence at 10 years by KM analysis *p<0.05, **p<0.005, ***p<.0005

Combining S-ODX with OPTIM, low (L) or high (H) risk by assay, shows that they are independent and complementary. Notably 68%=85/125 are classified L by S-ODX (RS<26) and OPTIM effectively reclassifies H and L, and when combined with S-ODX H identifies 92%=45/49 of all rMBC at 10 years without treatment. Risk stratification improves to 6.8X RR comparing highest risk HH 66.7%=12/18 to lowest risk LL 9.8%=4/41.

Distant Recurrence Identified by High Risk Group of Each Assay

S-ODX Assay
OPTIM Assay
rMBC (total=49) 12 14 19 
At Risk (total n=125) 18 22 44 41 
S-ODX Assay
OPTIM Assay
rMBC (total=49) 12 14 19 
At Risk (total n=125) 18 22 44 41 

rMBC at 10 yrs. S-ODX RS>25=H, RS<26=L; OPTIM Q1&Q2=H, Q3&Q4=L

Conclusion: OPTIM as an independent prognostic optical bio-marker from collagen in intact tissue. Combination of OPTIM with the Oncotype DX® assay may produce a continuous risk estimator with higher dynamic range than either assay alone and will be the focus of future study, especially in a treated population, to determine if OPTIM might also predict response to treatment.

Citation Format: Hill RL, Perry SW, Salzman P, Turner BM, Hicks DG, Brown EB. Optical Prediction of Time Interval to Metastasis (OPTIM): A rapid nondestructive optical assay applied to tissue microarray samples identifying high risk of distant recurrence in the lowest risk groups defined by the TAILORx trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-09-05.